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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
AMP-ACTIVATED KINASE PARTICIPATES IN CELL VOLUME REGULATION
Abstract number: P158
Föller
*M.
, Jaumann
3
M., Dettling
3
J., Saxena
1
A., Pakladok
1
T., Munoz
1
C., Alesutan
1
I., Singer
3
W., Ruth
4
P., Sopjani M., Seebohm
6
G., Rüttiger
3
L., Knipper
3
M., Lang
1
F.
1
Eberhard-Karls-University, Department of Physiology, Tuebingen, Germany
2
Ontario Cancer Institute, University Health Network (UHN), Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ontario
3
University of Tübingen, Department of Otolaryngology, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, Tübingen, Germany
4
University of Tübingen, Institute of Pharmacy, Department of Pharmacology and Toxicology, Tübingen, Germany
5
Faculty of Medicine, Prishtinë, Kosovo
6
Ruhr University Bochum, Biochemistry I, Bochum, Germany
Question:
AMP-dependent serine/threonine protein kinase (AMPK) is activated by cellular energy depletion or elevated cytosolic Ca2+ concentration. It promotes cellular energy production and limits cellular energy utilization. Cellular energy depletion may result in cell swelling due to decreased activity of Na+/K+ pump. We previously showed that AMPK counteracts cell swelling by inhibiting the activity of cellular osmolyte transporteres BGT and Smit. Here, we explored whether AMPK regulates the Ca2+-sensitive large conductance and voltage-gated potassium (BK) channel.
Methods:
cRNA encoding BK-channel was injected into Xenopus oocytes with and without additional injection of wild type AMPK (AMPKα1+AMPKβ1+AMPKγ1), constitutively active AMPKγR70Q, or inactive AMPKK45R. BK channel activity was determined utilizing the two-electrode voltage-clamp. Moreover, BK channel-protein abundance in the cell membrane was determined by chemiluminescence and confocal immunomicroscopy. As BK-channels are expressed in outer hair cells (OHC) of the inner ear and lack of BK-channels increases noise vulnerability, OHC BK-channel expression was examined by immunohistochemistry and hearing function analysed by auditory brain stem response measurements in AMPKα1-deficient mice (ampk-/-) and in wild type mice (ampk+/+).
Results:
Coexpression of AMPK or AMPKγR70Q but not of AMPKK45R significantly enhanced BK channel-mediated currents and BK channel protein abundance in the oocyte cell membrane. BK channel expression in the inner ear was lower in ampk-/-mice than in ampk+/+mice. The hearing thresholds prior to and immediately after an acoustic overexposure were similar in ampk-/- and ampk+/+mice. However, the recovery from the acoustic trauma was significantly impaired in ampk-/-mice compared to ampk+/+mice.
Conclusion:
AMPK is a potent regulator of BK-channels. It may thus participate in the signaling cascades that protect the inner ear from damage following acoustic overstimulation.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P158